This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. G-protein coupled receptors (GPCR) are the largest family of cell surface receptors and are responsible for the regulation of a myriad of processes in the human body including regulation of heart rate, blood pressure and glucose metabolism as well as the senses of sight and taste. Because of their central roles in cellular communication, GPCRs have been of fundamental interest in modern pharmacological research;e.g. approximately 50% of marketed drugs target GPCRs. In this proposal we will use the resources of Anton to explore the structure and functional consequences of water rearrangements in the signaling processes of GRPCs, using rhodopsin as our model system. This will help drive experiments to detect specific water rearrangements in GPCRs using novel mass spectrometry based technologies.